Exiting the RNA world

How did the first cells give rise to the three main branches of life? Two …

As we discussed yesterday, recent research has made the origin of a membrane-encased collection of nucleic acid catalysts look a lot less improbable than it did a few decades ago. Chronologically, the next outstanding question is how life on earth transitioned from these protocells to the major types of life we see today. Most of the work in that area focuses on the building of molecular trees, which help us identify the oldest genetic features that are common to most life, and thus are likely to have been present in the last common ancestor. We'll get into tree building separately, and focus here on two talks at the recent Rockefeller Symposium that took a different approach to the question.

One of them was from MIT's Phil Sharp, who won a Nobel Prize for his early work in RNA metabolism. Sharp's talk focused on RNA interference (RNAi), a set of several overlapping processes that use double-stranded RNAs to regulate gene expression. I'd seen proposals that suggested that RNAi evolved as a response to RNA-based viruses and transposons, but Sharp suggested that the process may be a remnant of the RNA world.

Part of his logic is that, in the RNA world, genetic regulation must have necessarily occurred through RNA-RNA interactions, so double-stranded RNAs may actually represent an ancestral form of gene regulation. He also pointed out that two of the proteins involved in RNAi processing, dicer and argonaute, appear to have been present in the ancestor of all Eukaryotes; argonaute also appears to be present in Archaeal and some Bacterial genomes. Other RNAi systems involve an RNA polymerase that uses RNA as a template. Sharp noted that this enzyme shares structural similarities with the major DNA replication enzymes, and suggested it may be ancestral to those.

There are a couple of problems with this proposal. Although most organisms seem to be capable of RNA interference, they don't all use the same systems, or even the same proteins to accomplish this. Many of the proteins involved have already been proposed to have evolved from other systems. Still, we're just beginning to understand the scope of RNA-based gene regulation, and it's possible that a clearer pattern—one more consistent with Sharp's proposal—will emerge once we understand it more fully. In the meantime, it's certainly worth keeping his ideas in mind since, if he's right, it will tell us a lot about how the first living organisms controlled their genes.

What did those first organisms look like? Thomas Cavalier-Smith thinks he knows and, based on his seminar, he's not shy of telling those who disagree with him that they're wrong. Cavalier-Smith thinks that trees based on DNA sequences are limited (a topic I'll return to later this week), and instead focuses on what he concludes are major changes in the basic chemistry of life. The reasoning is that these major changes required adaptation by many cellular components, and so are unlikely to have happened more than once.

In this line of reasoning, membranes are key. If a major change happens with membranes, any protein that sticks through them—pores, receptors, transporters, etc.—will have to adapt to those changes. Most of the big transitions outlined by Cavalier-Smith took place at the membrane, starting with a reduction of a two-membrane cell surface in the ancestral state down to a single cell membrane in most organisms alive today. The Archea and Eukaryotes then branched off the single-membrane lineage when they developed the capacity to link sugars to proteins as they're secreted across the membranes.

Instead of viewing the Eukaryotes as a branch of the Archea, he suggest the Archea are an outgroup, distinguished by a change in membrane chemistry when they started using etherlipids in their membranes. He suggested that this change necessitated the evolution of an entirely new flagella. Once the Archaea branched off, the remaining lineage generated the Eukaryotes. Cavalier-Smith wasn't against using molecular data—he tracked relationships between some Bacteria and Archaea via similarities in the proteasome—but it served primarily to supplement and inform the tree he constructed, rather than constrain it. Anyone interested in his model can read more details in an open access paper he's published (PDF).

Cavalier-Smith also touched on the origin of distinct Eukaryotic features, but those wound up the subject of two additional talks, so I won't cover that here. Even if his arguments turn out not carry the day in the scientific community, he sounded a worthwhile caution: too often, scientists focus on the math behind the trees they build, and forget to pay attention to the actual biology.